Comparative study about the therapeutic effect of cTBS and rTMS in the treatment of auditory verbal hallucinations in schizophrenia

Objective This study aims to compare the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) and continuous theta-burst stimulation (cTBS) treatment in schizophrenia patients with auditory verbal hallucinations (AVHs).Methods We enrolled 64 schizophrenia patients with AVHs who were treated with either rTMS (n = 32) or cTBS (n = 32), and we compared the clinical outcomes by evaluating parameters from motor evoked potentials, Positive and Negative Syndrome Scale (PANSS), Auditory Hallucination Rating Scale (AHRS), and MATRICS Consensus Cognitive Battery (MCCB), as well as the changes of serum neurotrophic factors before and after the treatment.Results After the treatment, both treatments resulted in reduced PANSS scores, with the cTBS group showing more substantial symptom improvement across positive, negative, and general symptoms, highlighting the enhanced efficacy of cTBS. Cognitive functions assessed by MCCB also improved in both groups, with cTBS showing a generally higher therapeutic effect. Serum levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) increased following treatment in both groups, with a more notable increase after cTBS, while GABA and glutamate levels remained unchanged. Cardiovascular indices were unaffected by either treatment, suggesting no significant impact on cardiovascular health.Conclusions Our study found that both rTMS and cTBS treatment can exhibit therapeutic effects in the management of AVHs in patients with schizophrenia. However, cTBS treatment generally shows a higher therapeutic effect than rTMS treatment. Key messages What is already known on this topic - rTMS and cTBS are noninvasive neuromodulation techniques used to treat AVHs in schizophrenia. Although both methods have shown some efficacy in reducing AVHs, previous studies suggest that cTBS may have more profound and lasting effects on cortical excitability than traditional rTMS. However, the therapeutic differences between cTBS and rTMS and their specific impacts on clinical symptoms, cognitive functions, and neurotrophic factors in patients with schizophrenia have not been thoroughly compared. What this study adds - This study demonstrates that both cTBS and rTMS can reduce symptoms of schizophrenia-related AVHs, but cTBS generally provides a greater therapeutic benefit. Compared to rTMS, cTBS was associated with more significant improvements in clinical symptoms assessed by PANSS and AHRS, as well as cognitive functions assessed by MCCB. Additionally, both treatments increased serum levels of BDNF and GDNF, with a more notable increase following cTBS, while levels of GABA and glutamate remained unchanged. How this study might affect research, practice or policy - The findings suggest that cTBS could be a more effective treatment option for AVHs in patients with schizophrenia, particularly patients who do not adequately respond to rTMS, potentially guiding clinical decisions on neuromodulation therapies. This study also underscores the need for further research to optimize cTBS protocols and explore its long-term efficacy and safety.